Owing to overexpression in a wide range of tumors, human epidermal growth factor receptor 2 (HER2) is one of the most utilized targeting antigens for antibody-drug conjugates (ADCs) to treat HER2-positive cancers. BOC Sciences provides the most complete set of solutions in ADC drug development services in the pharmaceutical industry. Working with companies and academic groups all over the world, including most of the top biopharmaceutical companies, our ADC technology supports the development and manufacture of antibody-drug conjugates. We are equipped with cGMP grade laboratory facilities and system, and our personnel is well versed in linker and cytotoxin conjugations technologies. We have a dedicated custom development platform that it’s very convenient for customers to customize different ADC products and services.
Human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor with a molecular mass of 185 kDa, is overexpressed in several cancers, such as breast, gastric, ovary, prostate, and lung. HER2 is a promising target in cancer therapy because of its crucial role in cell migration, proliferation, survival, angiogenesis, and metastasis through various intracellular signaling cascades. Given that all three domains of HER2 have significant role in the signaling pathway, each domain can be targeted independently to inhibit HER2 signaling. Strategies that have been utilized for targeting HER2 include mAbs, small-molecule tyrosine kinase inhibitors, ADCs, bispecific antibodies, and cellular-based therapies.
Fig. 1. Prevalence of HER2 amplification and overexpression in various tumors (Nat. Rev. Clin. Oncol. 2019, 17: 33-48).
Anti-HER2 antibodies can be conjugated with chemotherapeutic drugs, immunomodulators, as well as oligonucleotides, which in turn can augment their therapeutic efficacy as well as lead to reductions in chemotherapy-related adverse effects. ADCs are entities comprising an antibody linked to a therapeutic payload via either cleavable or noncleavable linkers. These ADCs are a smart treatment modality for HER2-positive cancer because of possible bystander effects. The success of these conjugates can be evidenced from the FDA approval of ado-trastuzumab emtansine (T-DM1, a FDA-approved ADC), which was developed by conjugating trastuzumab with a potent microtubule inhibitor, emtansine (DM1) via non-cleavable linkers, with an average drug antibody ratio of 3.5.
HER2-Targeted Therapy in Breast Cancer
Breast cancer is the most common malignancy threatening women's health worldwide. It affects approximately 1 in 8 women over the course of their lifetime and is also sometimes seen in men. One way to improve breast cancer treatment is designing drugs for targets with different expression levels on malignant cells and normal cells with the aim of improving tumor selectivity and reducing damage to normal tissues, such as HER2. The identification of HER2 as a target in breast cancer and the subsequent development of HER2-targeted therapies has revolutionized the treatment of patients with HER2-positive breast cancer. The clinical outcome of patients with HER2 amplified breast cancer has improved with the development of anti-HER2 targeted therapies.
HER2-Targeted Therapy in Gastric Cancer
Gastric cancer is one of the common malignancies in digestive tract tumors. According to the global cancer incidence and mortality statistics in 2020, there are more than 1000,000 new cases of gastric cancer and about 768,000 deaths. With the precision cancer medicine entering into clinical practice, the molecular targeted therapy of gastric cancer has attracted more and more attention, of which, HER2 has the clearest clinical significance and the most widely used. HER2-targeted ADCs are typical examples of HER2-targeted drugs with potentially more potent antitumoractivity in HER2-positive gastric cancer.
Fig. 2. Gastric cancer cells.
HER2-Targeted Therapy in Ovarian Cancer
Ovarian cancer is the deadliest of all gynecological malignancies with high mortality rate and high risk of drug resistance and recurrence after multiple rounds of chemotherapies. Several preclinical studies and clinical trials have evaluated the role of HER2-directed therapies in ovarian cancer. Among them, HER2 targeted therapy of ovarian cancer with the ADCs, is a promising drug delivery system, with a combination of antitumor activity and a desirable safety profile. Studies have shown that the conjugate is highly active at inhibiting tumor growth in HER2 positive ovarian cancer mouse models, and is well tolerated in rodent models.
HER2-Targeted Therapy in Lung Cancer
Lung cancer is the most malignant tumor in human. Therapeutic targeting of HER2 in lung cancers has been investigated for more than a decade. HER2 alterations have been identified as oncogenic drivers and potential therapeutic targets in lung cancers. HER2 mutations and HER2 amplifications have been reported in approximately 2% to 3% and 2% to 5% of lung adenocarcinomas, respectively. With a comprehensive antibody-drug conjugate platform, BOC Sciences provides one-stop ADC development services for HER2 targets to meet customer needs.
Currently, more than thirty anti-HER2 antibody-drug conjugate (ADC) candidates have entered clinical testing. BOC Sciences is one of the leaders in the field of biotherapeutic drug development. Our comprehensive ADCs system offers a wide range of ADCs design and construction services against the HER2-targeted therapy, including breast cancer, gastric cancer, ovarian cancer and lung cancer ect. Our services will assist customers in candidate selection and optimization in different phases of ADCs drug development. Our development services can not only speed up the commercial supply of products, but also have extremely high cost-effectiveness.